To date, a thorough understanding of one of the most basic functional capacities of the liver is lacking; namely, the mechanism(s) involved in bile secretion. This is especially true with regard to the morphological aspects of bile secretion. The research described in the protocol is designed to accomplish four major objectives: to definitively describe the morphological correlate of the hepatic bile secretory apparatus; 2) to establish the role(s) of intracellular vesicles and the Golgi complex in the secretion of bile; 3) to determine whether different components of bile, i.e. proteins and bile salts, are transported via similar or different pathways. In vivo and in vitro rat livers with perturbed bile synthesis or secretory rates will be critically evaluated by a variety of sophisticated morphologic criteria, including stereology, autoradiography, and cytochemistry. Our expertise in hepatic histology and cytology including electron microscopic autoradiography and in isolated liver perfusion techniques will be extremely useful in completing the study. Considerable interest will be directed towards the hepatocyte Golgi apparatus which is almost always polarized toward the bile canaliculus. We feel that our (1) observations of the Golgi complex migration and hypertrophy during enhanced bile secretion; (2) the accumulation of vesicles in the pericanalicular cytoplasm under similar conditions and (3) the identification of a liver cell vesicle transport system carrying both horseradish peroxidase and insulin from the blood to the bile provide an important first-step analysis of a complex problem.